Journal of pain research · 2026
LC-IL but Not LC-PL Circuit Regulates Comorbid Mechanical Hyperalgesia and Anxiety in Male Rats with Chronic Post-Surgical Pain.
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Lin Shenshen, Liu Congxu, Jiang Xiaoling, Lin Minyi, Wang Fengchai, Zhuo Yanmei, Lin Kaixing, Lin Chun, Liu Rongguo
Аннотация
OBJECTIVE: This study investigated the differential roles of Locus Coeruleus-Infralimbic cortex (LC-IL) and Locus Coeruleus-Prelimbic cortex (LC-PL) circuits in comorbid mechanical hyperalgesia and anxiety-like emotions in male rats with chronic post-surgical pain (CPSP).
METHODS: A total of 100 adult male Sprague-Dawley rats were randomly divided into 10 groups (n=10/group). Group included LC activation (sham+ChR2, sham+mch), LC-IL inhibition/activation (CPSP+NpHR, CPSP+mch; sham+ChR2, sham+mch), and LC-PL inhibition/activation (CPSP+NpHR, CPSP+mch; sham+ChR2, sham+mch). Using the skin/muscle incision and retraction procedure to establish CPSP or sham surgery. Optogenetic viruses (ChR2 for activation, NpHR for inhibition) or control virus (mCherry) were injected into the LC, with optical fibers implanted in the LC, IL, or PL. After 4 weeks of viral expression, blue or yellow light stimulation was applied. Mechanical paw withdrawal threshold was measured by Von-Frey filaments. Anxiety-like emotions was assessed by open field test and elevated plus maze.
RESULTS: Blue light irradiation of the LC region and LC-IL neural circuit both induced mechanical hyperalgesia and anxiety-like emotions in the rats. Yellow light irradiation of the LC-IL neural circuit alleviated mechanical hyperalgesia and anxiety-like emotions in CPSP model rats. Blue or yellow light irradiation of the LC-PL neural circuit had no significant effect on mechanical hyperalgesia or anxiety-like emotions in the rats.
CONCLUSION: The LC-IL circuit specifically regulates comorbid mechanical hyperalgesia and anxiety-like emotions in male CPSP rats, while the LC-PL circuit does not. These findings identify a sex-specific circuit mechanism and a potential therapeutic target for CPSP.
METHODS: A total of 100 adult male Sprague-Dawley rats were randomly divided into 10 groups (n=10/group). Group included LC activation (sham+ChR2, sham+mch), LC-IL inhibition/activation (CPSP+NpHR, CPSP+mch; sham+ChR2, sham+mch), and LC-PL inhibition/activation (CPSP+NpHR, CPSP+mch; sham+ChR2, sham+mch). Using the skin/muscle incision and retraction procedure to establish CPSP or sham surgery. Optogenetic viruses (ChR2 for activation, NpHR for inhibition) or control virus (mCherry) were injected into the LC, with optical fibers implanted in the LC, IL, or PL. After 4 weeks of viral expression, blue or yellow light stimulation was applied. Mechanical paw withdrawal threshold was measured by Von-Frey filaments. Anxiety-like emotions was assessed by open field test and elevated plus maze.
RESULTS: Blue light irradiation of the LC region and LC-IL neural circuit both induced mechanical hyperalgesia and anxiety-like emotions in the rats. Yellow light irradiation of the LC-IL neural circuit alleviated mechanical hyperalgesia and anxiety-like emotions in CPSP model rats. Blue or yellow light irradiation of the LC-PL neural circuit had no significant effect on mechanical hyperalgesia or anxiety-like emotions in the rats.
CONCLUSION: The LC-IL circuit specifically regulates comorbid mechanical hyperalgesia and anxiety-like emotions in male CPSP rats, while the LC-PL circuit does not. These findings identify a sex-specific circuit mechanism and a potential therapeutic target for CPSP.